This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 12/6/2007 Smoking is the single most preventable cause of morbidity and mortality in the United States. Indeed, smoking has been implicated in at least 30% of all cancer deaths in the U.S. and an estimated three million deaths per year worldwide. In spite of the clear negative consequences of smoking, a significant subset of the population continues to smoke. Moreover, although most smokers express a strong interest in quitting, few are successful at maintaining abstinence, a problem that is even more pronounced among women. Persistent smoking behavior (i.e., failure or difficulty in remaining abstinent) thus continues to be a major public health problem. Understanding the genetic and psychobiological determinants of smoking cessation success is a critical first step in developing novel approaches to promote cessation, so necessary to reduce the alarming rates of cancer and other smoking-related chronic diseases. The objective of this study is to characterize and better understand the effects of genetic polymorphisms in the dopamine system on stress- &smoking cue- induced cigarette cravings and smoking cessation among men who smoke. Grounded in a diverse literature, this multidisciplinary prospective study of men interested in making an untreated, 'cold turkey'smoking cessation attempt will provide a naturalistic look at potential effects of dopamine-related genotypes and stress- &cue-induced cravings elicited under laboratory conditions, on abstinence. To that end, 250 men will be genotyped for dopamine-related polymorphisms, participate in laboratory stress and cue-exposure tasks the day before their target quit date, and will be assessed for abstinence at 8 time points during a 6-month follow-up interval. By closely examining relations between experimentally-induced craving reactions and cessation, the study will attempt to better characterize mechanisms underlying the effects of dopamine genotypes. This study will lay the groundwork for larger-scale investigations aimed at determining the beneficial effects of tailored treatments (e.g., cue-exposure, stress management, nicotine replacement) in the context of genetic (e.g., dopamine polymorphisms) and psychobiological (e.g., cue- and stress-induced craving reactions) characteristics in samples of both men and women, with an eye toward yielding a better understanding of the unique challenges experienced by men trying to quit smoking. Hypothesis: Smokers carrying the risk polymorphisms will display higher levels of experimentally induced craving and, in turn, poorer cessation success than non-carriers.